Effects of pregnancy and nutritional status on alcohol metabolism

Alcohol Research & Health, Wntr, 2007 by Kartik Shankar, Martin J.J. Ronis, Thomas M. Badger

Metabolism of alcohol (i.e., ethanol) is regulated by genetic and environmental factors as well as physiologic state. For a given alcohol intake, the rate of alcohol clearance, which ultimately determines tissue ethanol concentrations, may be the most significant risk factor for many of the detrimental effects of alcohol. Faster ethanol clearance would help minimize target tissue concentrations, and in pregnant women, mitigate fetal alcohol exposure. Much remains to be known about the effects of the altered endocrine milieu of pregnancy on alcohol metabolism and clearance in the mother. Research has shown that among pregnant rats allowed unrestricted access to alcohol and those fed alcohol containing liquid diets under experimental conditions via a feeding tube (total enteral nutrition [TEN]), urine ethanol concentrations (and thus blood and tissue ethanol concentrations) are lower in pregnant rats compared with non-pregnant females given the same dose of ethanol. Maternal nutritional status also is an important determinant of fetal alcohol toxicity. Research using the TEN system has demonstrated that alcohol-induced fetal growth retardation is potentiated by undernutrition in part via impaired alcohol metabolism and clearance. KEY WORDS: Ethanol metabolism; ethanol clearance; pregnancy; maternal alcohol exposure; fetal alcohol effects; fetal alcohol spectrum disorder (FASD); alcohol-related birth defects (ARBD); nutrition; total enteral nutrition (TEN); maternal nutrition; genetic factors

ALCOHOL-RELATED BIRTH DEFECTS

Although the harmful effects of alcohol (i.e., ethanol) on the growing fetus have been recognized for nearly three decades, alcohol continues to be the most common malformation-causing chemical (i.e., teratogen) ingested during pregnancy (Randall 2001). One of every 29 women who know they are pregnant report alcohol consumption (Eustace et al. 2003). The toxic effects of in utero alcohol exposure are manifested by a constellation of physical, behavioral, and cognitive abnormalities commonly referred to as fetal alcohol spectrum disorder (FASD) or alcohol-related birth defects (ARBD). In addition to mental retardation, in utero alcohol exposure results in increased rates of miscarriage, reduced birth weight, growth retardation, and teratogenic effects (Jacobson et al. 1998). The incidence of FASD in the general U.S. population ranges from 0.7 to 10 cases per 1,000 live births annually (Eustace et al. 2003), which still is a surprisingly small proportion given the number of children exposed to alcohol during fetal development. The reasons for the low rate of FASD and precise mechanisms causing FASD remain elusive. This article examines the possible contributions of changes in alcohol metabolism during pregnancy and their interaction with maternal nutritional status in determining the degree to which alcohol is toxic to the fetus.

RODENT MODELS OF ALCOHOL CONSUMPTION IN PREGNANCY

Pregnancy presents a unique endocrine and metabolic circumstance not found in any other physiologic state with increased nutritional requirements. In addition, the physiologic and metabolic changes of pregnancy can result in altered metabolism of drugs and other chemicals that could result in altered drug efficacy (Ronis and Cunny 2001). Whereas much work has been conducted on the fetal effects of alcohol intake in humans and experimental rodent models, very little work has been published on maternal health related to alcohol intake during pregnancy. Furthermore, changes in maternal metabolism resulting from chronic ethanol intake during pregnancy have not been carefully explored and may have important implications in fetal alcohol exposure.

Rodents serve as good experimental models of human metabolic and endocrine events of pregnancy. By far, most studies of chronic alcohol effects in rodents have been conducted using alcohol-containing liquid diets, such as that developed by Lieber and DeCarli (1989). With few exceptions, laboratory rats, such as the Sprague-Dawley strain, have an aversion to alcohol-containing diets and typically consume 10 to 40 percent fewer calories than control rats given unrestricted access to food (i.e., ad libitum fed), resulting in lower body weight gains among the alcohol-fed rats (Rao and Larkin 1985; Fisher et al. 1997; Keiver et al. 1997). This makes it difficult to distinguish the effects of ethanol alone from the effects of a combination of alcohol and undernutrition. Animals fed the same amount of food as consumed by alcohol-fed rats (i.e., pair-fed controls) typically are used in an effort to account for the undernutrition caused by lower food intake.

Undernutrition is a particular problem in studies of alcohol consumption during pregnancy because of the increased nutrient requirements imposed by the growing fetal-placental unit. Feeding the Lieber-DeCarli diets to pregnant rodents resulted in an 18 to 50 percent reduction in gestational weight gain in pair-fed compared with ad libitum-fed mothers (i.e., dams) (Goad et al. 1984; Weinberg 1985; Keiver et al. 1997). This outcome is directly related to decreased dietary intake and is independent of ethanol consumption (Goad et al. 1984), highlighting the impact of decreased caloric intake of alcohol-containing diets.